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Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism's ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections.
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Etanolamina , Microbioma Gastrointestinal , Infecções por Klebsiella , Klebsiella pneumoniae , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/genética , Camundongos , Animais , Etanolamina/metabolismo , Microbioma Gastrointestinal/fisiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/metabolismo , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/metabolismo , Camundongos Endogâmicos C57BL , FemininoRESUMO
The global mid-ocean ridge system is the most extensive magmatic system on our planet and is the site of 75 per cent of Earth's volcanism1. The vertical extent of mid-ocean-ridge magmatic systems has been considered to be restricted: even at the ultraslow-spreading Gakkel mid-ocean ridge under the Arctic Ocean, where the lithosphere is thickest, crystallization depths of magmas that feed eruptions are thought to be less than nine kilometres2. These depths were determined using the volatile-element contents of melt inclusions, which are small volumes of magma that become trapped within crystallizing minerals. In studies of basaltic magmatic systems, olivine is the mineral of choice for this approach2-6. However, pressures derived from olivine-hosted melt inclusions are at odds with pressures derived from basalt major-element barometers7 and geophysical measurements of lithospheric thickness8. Here we present a comparative study of olivine- and plagioclase-hosted melt inclusions from the Gakkel mid-ocean ridge. We show that the volatile contents of plagioclase-hosted melt inclusions correspond to much higher crystallization pressures (with a mean value of 270 megapascals) than olivine-hosted melt inclusions (with a mean value of 145 megapascals). The highest recorded pressure that we find equates to a depth 16.4 kilometres below the seafloor. Such higher depths are consistent with both the thickness of the Gakkel mid-ocean ridge lithosphere and with pressures reconstructed from glass compositions. In contrast to previous studies using olivine-hosted melt inclusions, our results demonstrate that mid-ocean-ridge volcanoes may have magmatic roots deep in the lithospheric mantle, at least at ultraslow-spreading ridges.
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We recently described a simple model through which we assessed what effect subjecting travellers to a single on-arrival test might have on reducing risk of importing disease cases during simulated outbreaks of coronavirus disease 2019 (COVID-19), influenza, severe acute respiratory syndrome (SARS) and Ebola. We build upon this work to allow for the additional requirement that inbound travellers also undergo a period of self-isolation upon arrival, where upon completion the traveller is again tested for signs of infection prior to admission across the border. Prior results indicated that a single on-arrival test has the potential to detect 9% of travellers infected with COVID-19, compared to 35%, 10% and 3% for travellers infected with influenza, SARS and Ebola, respectively. Our extended model shows that testing administered after a 2-day isolation period could detect up to 41%, 97%, 44% and 15% of COVID-19, influenza, SARS and Ebola infected travellers, respectively. Longer self-isolation periods increase detection rates further, with an 8-day self-isolation period suggesting detection rates of up to 94%, 100%, 98% and 62% for travellers infected with COVID-19, influenza, SARS and Ebola, respectively. These results therefore suggest that testing arrivals after an enforced period of self-isolation may present a reasonable method of protecting against case importation during international outbreaks.
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COVID-19 , Doença pelo Vírus Ebola , Influenza Humana , COVID-19/diagnóstico , Surtos de Doenças/prevenção & controle , Humanos , Programas de RastreamentoRESUMO
This paper presents a method used to rapidly assess the incursion and the establishment of community transmission of suspected SARS-CoV-2 variant of concern Delta (lineage B.1.617.2) into the UK in April and May 2021. The method described is independent of any genetically sequenced data, and so avoids the inherent lag times involved in sequencing of cases. We show that, between 1 April and 12 May 2021, there was a strong correlation between local authorities with high numbers of imported positive cases from India and high COVID-19 case rates, and that this relationship holds as we look at finer geographic detail. Further, we also show that Bolton was an outlier in the relationship, having the highest COVID-19 case rates despite relatively few importations. We use an artificial neural network trained on demographic data, to show that observed importations in Bolton were consistent with similar areas. Finally, using an SEIR transmission model, we show that imported positive cases were a contributing factor to persistent transmission in a number of local authorities, however they could not account for increased case rates observed in Bolton. As such, the outbreak of Delta variant in Bolton was likely not a result of direct importation from overseas, but rather secondary transmission from other regions within the UK.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Surtos de Doenças , Humanos , SARS-CoV-2/genética , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To describe the clinical presentation, course of disease and health-care seeking behaviour of the first few hundred cases of coronavirus disease 2019 (COVID-19) in the United Kingdom of Great Britain and Northern Ireland. METHODS: We implemented the World Health Organization's First Few X cases and contacts investigation protocol for COVID-19. Trained public health professionals collected information on 381 virologically confirmed COVID-19 cases from 31 January 2020 to 9 April 2020. We actively followed up cases to identify exposure to infection, symptoms and outcomes. We also collected limited data on 752 symptomatic people testing negative for COVID-19, as a control group for analyses of the sensitivity, specificity and predictive value of symptoms. FINDINGS: Approximately half of the COVID-19 cases were imported (196 cases; 51.4%), of whom the majority had recent travel to Italy (140 cases; 71.4%). Of the 94 (24.7%) secondary cases, almost all reported close contact with a confirmed case (93 cases; 98.9%), many through household contact (37 cases; 39.8%). By age, a lower proportion of children had COVID-19. Most cases presented with cough, fever and fatigue. The sensitivity and specificity of symptoms varied by age, with nonlinear relationships with age. Although the proportion of COVID-19 cases with fever increased with age, for those with other respiratory infections the occurrence of fever decreased with age. The occurrence of shortness of breath also increased with age in a greater proportion of COVID-19 cases. CONCLUSION: The study has provided useful evidence for generating case definitions and has informed modelling studies of the likely burden of COVID-19.
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COVID-19/epidemiologia , COVID-19/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Dispneia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , SARS-CoV-2 , Viagem , Reino Unido/epidemiologia , Adulto JovemRESUMO
The effectiveness of screening travellers during times of international disease outbreak is contentious, especially as the reduction in the risk of disease importation can be very small. Border screening typically consists of travellers being thermally scanned for signs of fever and/or completing a survey declaring any possible symptoms prior to admission to their destination country; while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we describe a simple Monte Carlo based model that incorporates the epidemiology of coronavirus disease-2019 (COVID-19) to investigate the potential decrease in risk of disease importation that might be achieved by requiring travellers to undergo screening upon arrival during the current pandemic. This is a purely theoretical study to investigate the maximum impact that might be attained by deploying a test or testing programme simply at the point of entry, through which we may assess such action in the real world as a method of decreasing the risk of importation. We, therefore, assume ideal conditions such as 100% compliance among travellers and the use of a 'perfect' test. In addition to COVID-19, we also apply the presented model to simulated outbreaks of influenza, severe acute respiratory syndrome (SARS) and Ebola for comparison. Our model only considers screening implemented at airports, being the predominant method of international travel. Primary results showed that in the best-case scenario, screening at the point of entry may detect a maximum of 8.8% of travellers infected with COVID-19, compared to 34.8.%, 9.7% and 3.0% for travellers infected with influenza, SARS and Ebola respectively. While results appear to indicate that screening is more effective at preventing disease ingress when the disease in question has a shorter average incubation period, our results suggest that screening at the point of entry alone does not represent a sufficient method to adequately protect a nation from the importation of COVID-19 cases.
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COVID-19/diagnóstico , COVID-19/transmissão , Programas de Rastreamento , SARS-CoV-2 , Viagem , COVID-19/prevenção & controle , Humanos , Modelos Biológicos , Método de Monte Carlo , Fatores de RiscoRESUMO
Dose-response modeling of biological agents has traditionally focused on describing laboratory-derived experimental data. Limited consideration has been given to understanding those factors that are controlled in a laboratory, but are likely to occur in real-world scenarios. In this study, a probabilistic framework is developed that extends Brookmeyer's competing-risks dose-response model to allow for variation in factors such as dose-dispersion, dose-deposition, and other within-host parameters. With data sets drawn from dose-response experiments of inhalational anthrax, plague, and tularemia, we illustrate how for certain cases, there is the potential for overestimation of infection numbers arising from models that consider only the experimental data in isolation.
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Detecting rare species is important for both threatened species management and invasive species eradication programs. Conservation scent dogs provide an olfactory survey tool that has advantages over traditional visual and auditory survey techniques for some cryptic species. From the literature, we identified 5 measures important in evaluating the use of scent dogs: precision, sensitivity, effort, cost, and comparison with other techniques. We explored the scale at which performance is evaluated and examined when field testing under real working conditions is achievable. We also identified cost differences among studies. We examined 61 studies published in 1976-2018 that reported conservation dog performance, and considered the inconsistencies in the reporting of scent dog performance among these studies. The majority of studies reported some measure of performance; however, only 8 studies reported all 3 aspects necessary for performance evaluation: precision, sensitivity, and effort. Although effort was considered in 43 studies, inconsistent methods and incomplete reporting prevented meaningful evaluation of performance and comparison among studies. Differences in cost between similar studies were influenced by geographical location and how the dog and handler were sourced for the study. To develop consistent reporting for evaluation, we recommend adoption of sensitivity, precision, and effort as standard performance measures. We recommend reporting effort as the total area and total time spent searching and reporting sensitivity and precision as proportions of the sample size. Additionally, reporting of costs, survey objectives, dog training and experience, type of detection task, and human influences will provide better opportunities for comparison within and among studies.
Evaluación del Uso de Perros en la Conservación para la Búsqueda de Especies Raras Resumen La detección de las especies raras es importante tanto para el manejo de especies amenazadas como para los programas de erradicación de especies invasoras. Los perros usados para la conservación proporcionan una herramienta de censo olfativo que presenta algunas ventajas sobre las técnicas de censos visuales y auditivos usados para algunas especies crípticas. Identificamos cinco medidas importantes para la evaluación del uso de perros a partir de la literatura: precisión, sensibilidad, esfuerzo, costo y comparación con otras técnicas. Exploramos la escala a la cual se evalúa el desempeño y examinamos cuando son alcanzables las pruebas de campo bajo condiciones de trabajo reales. Examinamos 61 estudios publicados entre 1976 y 2018, los cuales reportaron sobre el desempeño de los perros para la conservación y consideramos las incongruencias en el reporte del desempeño de perros de olfato entre estos estudios. La mayoría de los estudios reportaron los tres aspectos necesarios para la evaluación del desempeño: precisión, sensibilidad y esfuerzo. Aunque 43 estudios consideraron al esfuerzo, los métodos incongruentes y el reporte incompleto impidieron una evaluación significativa del desempeño y una comparación entre los estudios. Las diferencias en el costo entre estudios similares estuvieron influenciadas por la ubicación geográfica y cómo el perro y su adiestrador fueron seleccionados para el estudio. Para desarrollar un reporte coherente para la evaluación, recomendamos la adopción de la sensibilidad la precisión y el esfuerzo como medidas estandarizadas del desempeño. Recomendamos que se reporte el esfuerzo como el área y el tiempo invertido en la búsqueda y la precisión como las proporciones del tamaño de la muestra. Además, el reporte de los costos, los objetivos de los censos, el entrenamiento y experiencia del perro, el tipo de labor de detección y la influencia humana proporcionarán mejores oportunidades para comparar dentro de un estudio o entre los estudios.
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Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Animais , Cães , HumanosRESUMO
Crystal mush is rapidly emerging as a new paradigm for the evolution of igneous systems. Mid-ocean ridges provide a unique opportunity to study mush processes: geophysical data indicate that, even at the most magmatically robust fast-spreading ridges, the magma plumbing system typically comprises crystal mush. In this paper, we describe some of the consequences of crystal mush for the evolution of the mid-ocean ridge magmatic system. One of these is that melt migration by porous flow plays an important role, in addition to rapid, channelized flow. Facilitated by both buoyancy and (deformation-enhanced) compaction, porous flow leads to reactions between the mush and migrating melts. Reactions between melt and the surrounding crystal framework are also likely to occur upon emplacement of primitive melts into the mush. Furthermore, replenishment facilitates mixing between the replenishing melt and interstitial melts of the mush. Hence, crystal mushes facilitate reaction and mixing, which leads to significant homogenization, and which may account for the geochemical systematics of mid-ocean ridge basalt (MORB). A second consequence is cryptic fractionation. At mid-ocean ridges, a plagioclase framework may already have formed when clinopyroxene saturates. As a result, clinopyroxene phenocrysts are rare, despite the fact that the vast majority of MORB records clinopyroxene fractionation. Hence, melts extracted from crystal mush may show a cryptic fractionation signature. Another consequence of a mush-dominated plumbing system is that channelized flow of melts through the crystal mush leads to the occurrence of vertical magmatic fabrics in oceanic gabbros, as well as the entrainment of diverse populations of phenocrysts. Overall, we conclude that the occurrence of crystal mush has a number of fundamental implications for the behaviour and evolution of magmatic systems, and that mid-ocean ridges can serve as a useful template for trans-crustal mush columns elsewhere. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.
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Textures and compositions of minerals can be used to infer the physiochemical conditions present within magmatic systems. Given that plagioclase is an abundant phase in many magmatic systems, understanding the link between texture and process is vital. Here, we present a database of textural and compositional data for > 1800 plagioclase crystals in mid-ocean ridge basalt from the Gakkel Ridge (Arctic Ocean) to investigate the physiochemical conditions and processes that govern the formation of plagioclase textures and compositions. The Gakkel basalts have high modal crystal contents (up to 50%). The crystal cargo is complex, with both individual plagioclase and glomerocrysts showing large variations in crystal habit, zoning and resorption. The most common types of zoning are reverse and patchy; we attribute patchy zoning to infilling following either skeletal growth or resorption. Resorption is abundant, with multiple resorption events commonly present in a single crystal, and results from both magmatic recharge and decompression. Periods of strong undercooling, distinct to quench crystallisation, are indicated by matured skeletal crystals and thin normally zoned melt inclusion-rich bands following resorption. Individual samples often contain diverse textural and compositional plagioclase groups. Furthermore, most plagioclase is not in equilibrium with its host melt. Finally, the porous open structures of some glomerocrysts suggest that they represent pieces of entrained disaggregated mush. We interpret this to indicate that the crystal cargo is not generally phenocrystic in origin. Instead, plagioclase crystals that formed in different parts of a mush-dominated plumbing system were entrained into ascending melts. The textures of individual crystals are a function of their respective histories of (under)cooling, magma mixing and decompression. The morphologies of melt inclusion trapped in the plagioclase crystals are associated with specific host crystal textures, suggesting a link between plagioclase crystallisation processes and melt inclusion entrapment. The database of plagioclase presented herein may serve as a template for the interpretation of plagioclase textures in magmatic systems elsewhere.
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RATIONALE AND KEY POINTS: This article explains how to prepare and administer an intravenous (IV) infusion using a gravity administration (giving) set or a volumetric pump in a safe, effective manner. Nurses undertaking this procedure must ensure they have the knowledge and skills to do so and work within the limits of their competence. This article serves as a revision of best practice in administering IV infusions of fluids and medicines. ⢠IV infusions are delivered directly into the bloodstream, so care must be taken to protect the patient from harm by following the appropriate policies and protocols and monitoring the patient carefully for adverse reactions. ⢠There is a risk of administering large volumes of IV fluid to the patient when using a gravity administration set, so a burette or volumetric pump should be used in patients who may not tolerate this. ⢠Volumetric pumps vary, so it is essential that the nurse is familiar with the device, uses the specific administration set required and follows the manufacturer's instructions. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: ⢠How this article might improve your practice when preparing and administering an IV infusion. ⢠How you could use this information to educate nursing students or your colleagues on the appropriate methods for preparing and administering an IV infusion.
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Bombas de Infusão , Infusões Intravenosas/métodos , Infusões Intravenosas/instrumentação , Humanos , Reino Unido , Gravitação , Competência ClínicaRESUMO
Lead (Pb) toxicity, through ingestion of lead ammunition in carcasses, is a threat to scavenging birds worldwide, but has received little attention in Australia. We analyzed lead exposure in the wedge-tailed eagle (Aquila audax), the largest raptor species found in mainland Australia and a facultative scavenger. Eagle carcasses were collected opportunistically throughout south-eastern mainland Australia between 1996 and 2022. Lead concentrations were measured in bone samples from 62 animals via portable X-ray fluorescence (XRF). Lead was detected (concentration >1 ppm) in 84% (n = 52) of the bone samples. The mean lead concentration of birds in which lead was detected was 9.10 ppm (±SE 1.66). Bone lead concentrations were elevated (10-20 ppm) in 12.9% of samples, and severe (>20 ppm) in 4.8% of samples. These proportions are moderately higher than equivalent data for the same species from the island of Tasmania, and are comparable to data from threatened eagle species from other continents. Lead exposure at these levels is likely to have negative impacts on wedge-tailed eagles at the level of the individual and perhaps at a population level. Our results suggest that studies of lead exposure in other Australian avian scavenger species are warranted.
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Águias , Intoxicação por Chumbo , Animais , Chumbo/análise , Austrália , ArmasRESUMO
The distribution of nutrients and assimilates in different organs and tissues is in a constant state of flux throughout the growth and development of a plant. At key stages during the life cycle profound changes occur, and perhaps one of the most critical of these is during seed filling. By restricting the competition for reserves in Arabidopsis plants, the ability to manipulate seed size, seed weight, or seed content has been explored. Removal of secondary inflorescences and lateral branches resulted in a stimulation of elongation of the primary inflorescence and an increase in the distance between siliques. The pruning treatment also led to the development of longer and larger siliques that contained fewer, bigger seeds. This seems to be a consequence of a reduction in the number of ovules that develop and an increase in the fatty acid content of the seeds that mature. The data show that shoot architecture could have a substantial impact on the partitioning of reserves between vegetative and reproductive tissues and could be an important trait for selection in rapid phenotyping screens to optimize crop performance.
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Desenvolvimento Vegetal , Plantas/metabolismo , Cruzamento , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismoRESUMO
Introduction: Following the easing of COVID-19 restrictions in many countries, a surge in respiratory syncytial virus (RSV) hospitalisations was reported, surpassing yearly trends pre-pandemic. The changes to RSV epidemiology may have unforeseen effects on healthcare systems and populations globally, adding to the burden generated during the pandemic and placing increased demand on resources. Here we aim to identify recent global trends of RSV hospitalisation amongst children aged ≤5â years, to help inform policy makers in the planning of preventative interventions. Methods: We conducted a scoping review of published literature between January 2009 and May 2021. Using keywords "Hospital admissions, Respiratory syncytial virus, RSV, Bronchiolitis, Children" we located studies using Medline, EMCARE, CINAHL and HMIC. Studies were eligible if they reported on trends/data for RSV hospitalisation amongst children aged ≤5â years. The articles were reviewed by two independent reviewers. Findings: We assessed 3310 abstracts, reviewed 70 studies and included 56 studies in the final review. Findings were categorised into themes. The review highlighted that, although RSV incidence has been steadily increasing since 2009, the number of reported RSV hospitalisations decreased during lockdown. The highest numbers of hospitalisations were reported in children <1â year of age, particularly 0-2-month-old infants. Globally, RSV hospitalisations tend to peak in the winter months; however, since COVID-19 restrictions have eased, countries are reporting incidence peaks at different times, in contrast to the trends of previous years. Conclusion: With greater physical interactions due to the relaxation of COVID-19 restriction measures, RSV-related hospitalisations can be seen to increase amongst children aged ≤5â years, possibly surpassing the numbers reported in previous RSV seasons.
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Objectives: Paediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases. Methods: SARS-CoV-2 infections in CYP aged 0-15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections. Results: During the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037-0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025-0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model. Conclusions: The model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant.
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Pods play a key role in encapsulating the developing seeds and protecting them from pests and pathogens. In addition to this protective function, it has been shown that the photosynthetically active pod wall contributes assimilates and nutrients to fuel seed growth. Recent work has revealed that signals originating from the pod may also act to coordinate grain filling and regulate the reallocation of reserves from damaged seeds to those that have retained viability. In this review we consider the evidence that pods can regulate seed growth and maturation, particularly in members of the Brassicaceae family, and explore how the timing and duration of pod development might be manipulated to enhance either the quantity of crop yield or its nutritional properties.
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Brassicaceae/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/metabolismo , Sementes/crescimento & desenvolvimento , Transporte Biológico , Brassicaceae/metabolismo , Nitrogênio/metabolismo , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento , Sementes/ultraestruturaRESUMO
To detect methicillin resistant Staphylococcus aureus (MRSA) and S. pseudintermedius (MRSP) swab samples were collected from dogs, cats and horses from South East Queensland (SE QLD). MRSP carriage in dogs was 8.7% and no MRSP was isolated from cats and horses; no MRSA was isolated. Risk factors for carriage included previous hospitalisation, previous bacterial infection, consultation type, average precipitation, and human population density. The probability of MRSP carriage was highest in Brisbane city, Sunshine Coast and Gympie. This suggests that MRSP carriage in dog populations from SE QLD is geographically clustered and associated with clinical and environmental factors.
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Doenças do Gato/epidemiologia , Doenças do Cão/epidemiologia , Doenças dos Cavalos/epidemiologia , Infecções Estafilocócicas/veterinária , Animais , Doenças do Gato/microbiologia , Gatos , Doenças do Cão/microbiologia , Cães , Feminino , Doenças dos Cavalos/microbiologia , Cavalos , Masculino , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/fisiologia , Queensland/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/fisiologiaRESUMO
Early assessments of the growth rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but as cases were recorded in multiple countries, more robust inferences could be made. Using multiple countries, data streams and methods, we estimated that, when unconstrained, European COVID-19 confirmed cases doubled on average every 3 days (range 2.2-4.3 days) and Italian hospital and intensive care unit admissions every 2-3 days; values that are significantly lower than the 5-7 days dominating the early published literature. Furthermore, we showed that the impact of physical distancing interventions was typically not seen until at least 9 days after implementation, during which time confirmed cases could grow eightfold. We argue that such temporal patterns are more critical than precise estimates of the time-insensitive basic reproduction number R0 for initiating interventions, and that the combination of fast growth and long detection delays explains the struggle in countries' outbreak response better than large values of R0 alone. One year on from first reporting these results, reproduction numbers continue to dominate the media and public discourse, but robust estimates of unconstrained growth remain essential for planning worst-case scenarios, and detection delays are still key in informing the relaxation and re-implementation of interventions. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.
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COVID-19/epidemiologia , Modelos Teóricos , Pandemias , COVID-19/virologia , Humanos , Itália/epidemiologia , Distanciamento Físico , SARS-CoV-2RESUMO
Senescent cells contribute to pathology and dysfunction in animal models1. Their sparse distribution and heterogenous phenotype have presented challenges for detecting them in human tissues. We developed a senescence eigengene approach to identify these rare cells within large, diverse populations of postmortem human brain cells. Eigengenes are useful when no single gene reliably captures a phenotype, like senescence; they also help to reduce noise, which is important in large transcriptomic datasets where subtle signals from low-expressing genes can be lost. Each of our eigengenes detected ~2% senescent cells from a population of ~140,000 single nuclei derived from 76 postmortem human brains with various levels of Alzheimer's disease (AD) pathology. More than 97% of the senescent cells were excitatory neurons and overlapped with tau-containing neurofibrillary tangles (NFTs). Cyclin dependent kinase inhibitor 2D (CDKN2D/p19) was predicted as the most significant contributor to the primary senescence eigengene. RNAscope and immunofluorescence confirmed its elevated expression in AD brain tissue whereby p19-expressing neurons had 1.8-fold larger nuclei and significantly more cells with lipofuscin than p19-negative neurons. These hallmark senescence phenotypes were further elevated in the presence of NFTs. Collectively, CDKN2D/p19-expressing neurons with NFTs represent a unique cellular population in human AD with a senescence phenotype. The eigengenes developed may be useful in future senescence profiling studies as they accurately identified senescent cells in snRNASeq datasets and predicted biomarkers for histological investigation.